MSI1 promotes the expression of the GBM stem cell marker CD44 by impairing miRNA-dependent degradation

Rebecca Pötschke, Jacob Haase, Markus Glaß, Sebastian Simmermacher, Claudia Misiak, Luiz O.F. Penalva, Caspar D. Kühnöl, Stefan Hüttelmaier

Research output: Contribution to journalArticlepeer-review

Abstract

The stem cell marker Musashi1 (MSI1) is highly expressed during neurogenesis and in glioblastoma (GBM). MSI1 promotes self-renewal and impairs differentiation in cancer and non-malignant progenitor cells. However, a comprehensive understanding of its role in promoting GBM-driving networks remains to be deciphered. We demonstrate that MSI1 is highly expressed in GBM recurrences, an oncologist’s major defiance. For the first time, we provide evidence that MSI1 promotes the expression of stem cell markers like CD44, co-expressed with MSI1 within recurrence-promoting cells at the migrating front of primary GBM samples. With GBM cell models of pediatric and adult origin, including isolated primary tumorspheres, we show that MSI1 promotes stem cell-like characteristics. Importantly, it impairs CD44 downregulation in a 3 UTR-and miRNA-dependent manner by controlling mRNA turnover. This regulation is disturbed by the previously reported MSI1 inhibitor luteolin, providing further evidence for a therapeutic target potential of MSI1 in GBM treatment.

Original languageEnglish (US)
Article number3654
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume12
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • CD44
  • Cancer stem cell
  • GBM
  • Glioblastoma
  • Luteolin
  • MSI1
  • MiRNA
  • Musashi1
  • Recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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